IntroductionThe experience of cancer among relatives is characterized by an increase in anxiety and depression, stress, and a reduction in quality of life. However, there is a paucity of psychosocial support programmes for relatives and a dearth of evidence-based, manualized interventions. Accordingly, the present study aims to assess the acceptability, defined as participant drop-out and satisfaction, and feasibility, in terms of mental health improvement, of a novel manualized psycho-educational group intervention.MethodsThe manual was developed on the basis of previous research into psychotherapy. A total of 33 relatives of cancer patients were recruited from the West German Tumor Center and participated in the five modules of the RELIEVE treatment which included an introduction, communication skills, stress and anxiety management and self-care. The primary outcome was assessed using a range of measures, including anxiety (GAD-7), depression (PHQ-8), stress (PSQ), self-efficacy (SES), need for support (SCNSP&C-G), and quality of life (WGOQOL-BREF) before and after the completion of the treatment programme. A paired samples T-test was employed to assess the feasibility of the treatment, with pre- and post-scores being compared. The secondary outcome of treatment acceptance was evaluated by calculating the drop-out rate and scoring a treatment satisfaction questionnaire.ResultsA high level of satisfaction was reported by participants. The drop-out rate for the treatment was minimal, at only 2.86%. Following the completion of the treatment programme, there were significant improvements in anxiety, depression and stress scores, as well as an improvement in quality of life. No significant improvements were observed in self-efficacy, work and social security needs, and quality of life in the social relationships domain.DiscussionThe RELIEVE intervention demonstrated high feasibility and acceptance among emotionally affected relatives of cancer patients, addressing a gap in previous interventions that were often limited in scope and lacked standardised manuals.ConclusionThis feasibility study on treatment acceptance underlines the importance of measures that are tailored to the specific needs of cancer patients’ relatives, and of integrating them into the general healthcare system.

Background: The overall level of physical and psychological symptom burden of advanced cancer patients (ACP) in an outpatient setting is notoriously difficult to assess. Therefore, more efficient and objective assessment is needed to accomplish this important task. Objectives: The aim of this study was to compare the physical and psychological symptom burden rated by palliative care nurse (PCN) versus patient?s self-rating. Design: This retrospective German cohort study analyzed symptom burden using an electronic patient-reported outcome measure (ePROM). After referral to an outpatient specialized palliative care team, a PCN assessed the patient?s symptoms both up to three months before initial presentation (IP) and at IP. Group differences were identified using analyses of variance (ANOVA). Further descriptive analysis of patient characteristics was used. Subjects: The study enrolled 164 ACP who were referred to a specialized palliative care (SPC) team. Mean age was 62 (? 12.6) years. Gastrointestinal (n = 46; 28.0%), lung (n = 32; 19.5%), and breast cancer (n = 34; 20.7%) were the most common entities. Results: Most frequent reasons for referral were pain (n = 55; 33.5%) and social care problems (n = 36; 22.0%). Patients reported significantly higher grades on depression (n = 144; Z = ?2.8, p = 0.005), anxiety (n = 144; Z = ?2.376, p = 0.018), and worsened general condition (n = 139; Z = ?7.005, p < 0.001). Conclusion: ACP in an outpatient setting were more frequently referred to SPC for pain management and assistance with social problems with regard to the cancer and its limitations. Psychological distress was underrated by the PCN in comparison with patient self-reporting through ePROM. This underlines the importance of self-reported outcome measurement.

Objective(s) Differences in the German emergency medical service (EMS) can be seen in the countryside in contrast to the city with regard to travel distances to hospitals and in the access routes of EMS-physicians. In order to investigate the success of establishment of palliative crisis cards associated with training and the rural and urban EMS structures, two urban and two rural EMS areas were compared using the Paramedic Palliative Care Test (PARPACT). Methods: The PARPACT includes test items on palliative knowledge (PK, maximum score: 15 points) and palliative self-efficacy expectations (PSE, maximum score: 18 points), as well as items on palliative attitudes in dealing with palliative care patients. We used a 4-point Likert-type scale. For data analysis, nonparametric tests (χ-test and Mann–Whitney U test) were used in addition to descriptive analysis (frequencies, means, medians, standard deviations, and ranges). Results: In total, 291 out of 750 ambulance or EMS personnel participated in the voluntary survey. Rural ambulance or EMS personnel answered the PK-questions correctly more often on average (mean: 11.19, SD: 1.85) than urban ambulance or EMS personnel (mean: 9.18, SD: 2.39; Mann–Whitney U test: U=5040.000, P=.001). In addition, ambulance or EMS personnel with the highest level of training (3-year-trained paramedics) performed better in PK (mean: 10.38, SD: 2.31) than less intensively training ambulance or EMS personnel (mean: 9.58, SD: 2.43; Mann-Whitney U-test: U=8446.500, P=.004). In terms of PSE, rural ambulance or EMS personnel also achieved higher mean PSE-scores (mean: 12.55, SD: 2.60) than urban ambulance or EMS personnel (mean: 9.77, SD: 3.41; Mann-Whitney U-test: U=5148.500, P=.001). Conclusions: Better training in the EMS is associated with improved PK compared to less qualified nonphysician EMS staff. The establishment of palliative crisis cards and the structures in the city alone do not lead to improved knowledge and PSE.

Purpose: Disturbances of electrolytes and renal function have been linked to the prognosis of critically ill patients and recently also of cancer patients. This study aimed to assess electrolyte and renal disorders in glioblastoma patients and evaluate their prognostic effect. Methods: Medical records of patients with newly diagnosed glioblastoma between 2005 and 2018 were retrospectively reviewed for electrolyte and renal function parameters and for demographic, clinical and outcome parameters. Results: Electrolyte and renal function disorders were associated with poorer survival in univariate and Kaplan-Meier analysis. Multivariate analysis revealed hypochloremia as an independent prognostic factor for overall and 1-year survival. Conclusion: Only hypochloremia showed an association with glioblastoma prognosis, independent of other known prognostic factors, as age or molecular status.

BACKGROUND: Hormone and human epidermal growth factor receptor 2 (HER2/neu) receptor status is prognostic and predictive in breast cancer (BC) and guides the choice of therapy. However, owing to receptor conversion, the receptor status can differ in metastases compared with that of the primary tumor. The aim of the present study was to analyze the prognostic value of receptor status, receptor conversion, and clinical parameters in patients with resected BC brain metastases (BMs). METHODS: Patients with BCBMs treated at our institution from July 2007 to December 2019 were eligible for the present study. The receptor status of the BC and corresponding BMs and the occurrence of receptor conversion were separately recorded for 3 common receptors: HER2/ neu, estrogen receptor, and progesterone receptor. The association between the receptor status or receptor conversion and clinical parameters was adjusted for outcome relevant patient and tumor characteristics. RESULTS: The final analysis included 78 patients. HER2/ neu receptor status in BMs was associated with overall survival (P = 0.033). Receptor conversion was identified in 39 patients (50.0%): HER2/neu, n = 9 (11.5%); estrogen receptor, n = 22 (28.2%); and progesterone receptor, n = 25 (32.1%). In the final multivariate Cox regression analysis, HER2/neu receptor conversion (adjusted hazard ratio [aHR], 3.58; P = 0.006), Karnofsky performance status score <70% (aHR, 3.11; P = 0.048), infratentorial BM location (aHR, 2.49; P = 0.007), and age double dagger 55 years at BM diagnosis (aHR, 2.20; P = 0.046) were independently associated with poorer survival. CONCLUSIONS: Of the 3 common BC receptors, only HER2/neu receptor conversion was strongly associated with the prognosis of patients with surgically treated BCBMs. The clinical relevance of the reevaluation of receptor status in BMs favors surgical treatment of patients with noneloquent BCBMs.

Background: Histologic transformation (HT) of indolent B-cell lymphomas into an aggressive form can occur simultaneously (primary HT, pHT) or sequentially after a preceding diagnosis of indolent lymphoma (secondary HT, sHT). The clinical course after diagnosis of HT is variable. Objectives: To describe the outcome of treatment in pHT and sHT patients. Methods: We retrospectively analyzed HT cases with an underlying follicular lymphoma, nodal marginal zone lymphoma, extranodal marginal zone lymphoma, lymphoplasmacytic lymphoma, or small lymphocytic lymphoma at our institution. Kaplan-Meier estimates were used to calculate progression-free survival (PFS) and overall survival (OS). Results: Ninety-two HT patients were identified, 38 with pHT and 54 with sHT. In sHT, time-to-transformation was not influenced by the preceding treatment strategy of the indolent lymphoma component. In pHT, median PFS was 61 months (95% CI 27-61), and OS was not reached. In sHT, median PFS and OS was 14 months (95% CI 9-32) and 42 months (95% CI 16-90), respectively. Significant differences between pHT and sHT in PFS (p = 0.002; Hazard ratio [HR] 2.30, 95% CI 1.36-3.91) and OS (p = 0.0001; HR 3.30, 95% CI 1.81-6.03) were observed. Response to treatment for transformation was highly prognostic of PFS and OS (p < 0.0001). Conclusions: The outcome in pHT cases is favorable and signifi-cantly better than in sHT cases. Failure to achieve a remission after treatment for transformation confers a dismal pro-gnosis.

Background: In Germany, some units of specialized palliative care (SPC) offer a 6- to 12-month rotation for resident physicians (RPs) and fellows from different specialties. Objective: This pilot study aimed to evaluate feasibility of assessing palliative care knowledge (PCK) and palliative care self-efficacy (PCSE) using a paper-based questionnaire. Methods: Palliative care knowledge and PCSE were assessed by introducing a score, followed by a descriptive analysis (determination of frequency, mean, median, and range) using nonparametric tests (χ2 test, Mann–Whitney U test). Results: We assessed 17 RPs following SPC rotation and 16 board-certified specialists (BCSs) who had no experience in SPC from 3 German comprehensive cancer centers. Resident physicians were predominantly enrolled in residency programs of hematology and oncology (n = 6), anesthesiology (n = 6), and psychosomatic medicine (n = 3). Resident physicians rotated between year 1 and 8 of residency. Fifteen RPs (88%) had elected this rotation and 72% preferred 12-month duration. The total PCK score of PCK was 27 (RPs) and 24 (BCSs; P = .002). Mean PCSE scores were 46 (RPs) and 39 (BCSs; P = .016). Of 71% of RPs, only 27% of BCSs knew how support of hospice service was initiated (P = .004). Participants rated the items as comprehensible (n = 24; 73%), relevant (n = 25; 76%) and the questionnaire as adequately long (n = 23; 70%). Conclusion: An improved PCK and PCSE were observed in physicians who rotated through an SPC unit; this resulted in an increased tangibility of local palliative care and hospice services. The questionnaire was comprehensible, relevant in terms of content, and adequate in length for a prospective multicenter survey.

We studied the effect of MET expression in a prospectively recruited cohort of patients (n = 384) with advanced nonesmall-cell lung cancer (NSCLC). High MET expression was associated with inferior outcome of epidermal growth factor receptor-targeting therapy, but with a more favorable outcome with programmed death 1/programmed death ligand 1-directed therapy. MET mutations were detected at low prevalence (0.78%) and MET-mutated NSCLC appeared-on an anecdotal basis-to respond less to immunotherapy. Background: The receptor tyrosine kinase MET is implicated in malignant transformation, tumor progression, metastasis, and acquired treatment resistance. We conducted an analysis of the effect of MET expression and MET genomic aberrations on the outcome of patients with advanced or metastatic pulmonary adenocarcinomas prospectively enrolled in an institutional precision oncology program. Patients and Methods: Standardized immunohistochemistry (IHC) analyses of MET and markers of pathway activation were available in 384 patients, and nextgeneration sequencing-based MET hotspot mutation analyses were available from 892 patients. Clinical data were retrieved with a median follow-up from initial diagnosis of 37 months. Results: High MET expression, defined as MET IHC 3+ or MET H-Score in the upper quartile, was observed in 102 of 384 patients (26.6%). MET exon 14 mutations were only detected in 7 of 892 patients (0.78%). High MET expression correlated with activation markers of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathways only in cases without Kirsten rat sarcoma viral oncogene homolog (KRAS), epidermal growth factor receptor (EGFR), v-Raf murine sarcoma viral oncogene homolog B (BRAF), anaplastic lymphoma kinase (ALK) and proto-oncogene tyrosine-protein kinase ROS (ROS1) aberrations. There was no association of MET expression with outcome during chemotherapy. High MET expression negatively affected the outcome during EGFR-targeting therapy but was associated with more favorable results with programmed death 1/programmed death ligand 1 (PD-L1)-directed therapy, independent of smoking history, PD-L1 expression or KRAS mutation. Two patients with MET exon 14 mutation and high PD-L1 expression failed to respond to pembrolizumab. Conclusion: MET expression affects the outcomes of targeted therapies in non-small-cell lung cancer, thus supporting the development of biomarker-informed combination strategies. The interaction of MET expression and MET mutation with immune checkpoint inhibitor therapy is novel and merits further investigation. (C) 2018 Elsevier Inc. All rights reserved.

The objective of this study was to evaluate the potential of integrated 11C-MET PET/MR for response assessment of relapsed glioblastoma (GBM) receiving bevacizumab treatment.

Introduction The objective of this study was to assess the diagnostic value of integrated 11C- methionine PET/MRI for suspected primary brain tumors, in comparison to MRI alone. Material and Methods Forty-eight consecutive patients with suspected primary brain tumor were prospectively enrolled for an integrated 11C-methionine PET/MRI. Two neuro-radiologists separately evaluated the MRI alone and the integrated PET/MRI data sets regarding most likely diagnosis and diagnostic confidence on a 5-point scale. Reference standard was histopathology or follow-up imaging. Results Fifty-one suspicious lesions were detected: 16 high-grade glioma and 25 low-grade glioma. Ten non-malignant cerebral lesions were described by the reference standard. MRI alone and integrated PET/MRI each correctly classified 42 of the 51 lesions (82.4%) as neoplastic lesions (WHO grade II, III and IV) or non-malignant lesions (infectious and neoplastic lesions). Diagnostic confidence for all lesions, low-grade astrocytoma and high-grade astrocytoma (3.7 vs. 4.2, 3,1 vs. 3.8, 4.0 vs. 4,7) were significantly (p < 0.05) better with integrated PET/MRI than in MRI alone. Conclusions The present study demonstrates the high potential of integrated 11C-methionine-PET/MRI for the assessment of suspected primary brain tumors. Although integrated methionine PET/MRI does not lead to an improvement of correct diagnoses, diagnostic confidence is significantly improved.

TPS2082 Background: Mutations in the gene for isocitrate dehydrogenase type 1 frequently occur in diffuse gliomas resulting in a point mutation (IDH1R132H) in most of the cases. Preclinical studies have shown that mutation-specific T helper (Th) cell responses spontaneously occur in patients with IDH1-mutated gliomas and that a peptide vaccine encoding IDH1R132H is therapeutic in a humanized mouse tumor model. Methods: NOA-16 (ClinicalTrials.gov Identifier: NCT02454634) is a multicenter, first-in-man, phase I clinical trial, which is planned to enroll 39 patients with newly diagnosed malignant astrocytomas with IDH1R132H mutations at eight German sites. The target population is molecularly enriched for an unfavorable prognosis within the IDH1-mutated subgroup by mandating (i) absence of co-deletion of 1p/19q and (ii) loss of alpha-thalassemia/mental retardation syndrome X-linked (ATRX) expression. Patients aged ≥ 18 years with a Karnofsky performance score of ≥ 70 will receive radiotherapy only (cohort 1), combined radiochemotherapy with temozolomide (TMZ, cohort 2) or TMZ only (cohort 3) as the primary treatment based on the decision of the local investigator. Over a period of 32 weeks a total of eight vaccinations with an IDH1R132H peptide emulsified in incomplete Freund's adjuvant produced at a central good manufacturing practice (GMP) site will be administered subcutaneously with topical imiquimod starting three months after the initiation of primary treatment. The primary end points are safety and immunogenicity as measured by IDH1R132H-specific antibody and T cell responses. Secondary outcome measures include progression-free survival (PFS) and overall response rate (ORR). Enrollment started in June 2015. The DMC reviewed the trial in December 2015 and suggested that the trial continues as planned after the first three patients had completed the first vaccinations without a regime-limiting toxicity (RLT). Eight patients have been enrolled at three sites (as of January 2016). Clinical trial information: NCT02454634.

Chemotherapy‐induced peripheral neuropathy ( CIPN ) lacks standardized clinical measurement. The objective of the current secondary analysis was to examine data from the CIPN Outcomes Standardization ( CI‐PeriNomS ) study for associations between clinical examinations and neurophysiological abnormalities. Logistic regression estimated the strength of associations of vibration, pin, and monofilament examinations with lower limb sensory and motor amplitudes. Examinations were classified as normal (0), moderately abnormal (1), or severely abnormal (2). Among 218 participants, those with class 1 upper extremity ( UE ) and classes 1 or 2 lower extremity ( LE ) monofilament abnormality were 2.79 (95% confidence interval [ CI ]: 1.28–6.07), 3.49 (95% CI : 1.61–7.55), and 4.42 (95% CI : 1.35–14.46) times more likely to have abnormal sural nerve amplitudes, respectively, compared to individuals with normal examinations. Likewise, those with class 2 UE and classes 1 or 2 LE vibration abnormality were 8.65 (95% CI : 1.81–41.42), 2.54 (95% CI : 1.19–5.41), and 7.47 (95% CI : 2.49–22.40) times more likely to have abnormal sural nerve amplitudes, respectively, compared to participants with normal examinations. Abnormalities in vibration and monofilament examinations are associated with abnormal sural nerve amplitudes and are useful in identifying CIPN .

2086 Background: Deregulation of the PI3K/AKT pathway has been preclinically involved in the pathophysiology of GBM. The mammalian target of rapamycin (mTOR) is an important downstream mediator of PI3K/AKT signalling. The mTOR-inhibitor temsirolimus (Tem) achieves significant drug levels in brain. Thus, Tem may be effectively combined with irinotecan (Iri) which has shown promising results in combination with bevacizumab in patients (pts) with reGBM refractory to temozolomide (Tmz) in phase II. Exposure to Tem as well as Iri is substantially reduced in pts receiving CYP3A4 enzyme-inducing anticonvulsants (CYP3A4-Ind). Methods: TEMIR is a phase I trial of escalating doses of Tem in combination with Iri in pts with reGBM refractory to Tmz depending on the cotreatment with CYP3A4-Ind. In pts without CYP3A4-Ind dose escalation of Tem was performed according to the “3+3 protocol” from 15 via 20 to 25 mg iv wkly together with 85 mg/m2 Iri iv wkly. In pts with CYP3A4-Ind the doses of Tem were 30, 40 and 50 mg iv wkly together with 170 mg/m2 Iri iv wkly, respectively. The determination of the pharmacokinetics (PK) of Tem and its influence on the PK of Iri and its active metabolite SN38 was performed by validated RP-HPLC methods with fluorescence detection. Results: Up to now, 14 pts [4 female and 10 male, median age 47 yrs (range 41-65 yrs), 9 without and 5 with CYP3A4-Ind] have been treated. All 9 pts without CYP3A4-Ind (3 pts on 15, 20 and 25 mg Tem each) are evaluable for safety with only mild toxicity [highest CTC-grade ≥2 (gr) per pt]: diarrhea 4 (gr2) and 1 (gr3), neutropenia 1 (gr3), thrombopenia 1 (gr2), anemia 1 (gr2), pneumonia 2 (gr2), rash 1 (gr2). PK parameters of Iri and SN38 were in agreement with previously published studies and there was no significant effect of 15 to 25 mg Tem combined with 85 mg/m2 Iri on the PK of Iri and SN38. In 7 pts evaluable for efficacy there was no remission (RECIST) and median time to symptomatic and/or MRT progression was 10 wks (7, 9+, 10, 10+, 11, 15, 20 wks). Conclusions: The combination of Tem in standard dose of 25 mg iv wkly with 85 mg/m2 Iri wkly is safe in pts with reGBM without CYP3A4-Ind. Tem has no significant effect on the PK of Iri and SN38.

Background: There is no effective systemic therapy for patients (pts) with metastatic uveal melanoma (metUvMel). Due to the paucity of clinical trials pts are frequently offered individual treatment options. We have analyzed the outcome of pts treated for metUvMel with the oral multikinase inhibitor sorafenib (S) in an IEC-approved register trial of the West German Cancer Center, a national reference center for uveal melanomas. Methods: Pts with metUvMel were treated with S [at a dose of 400 mg bid in the first group (G1) and of 200 mg bid in the second group (G2)]. Overall survival (OS) and time to symptomatic progression (TTPsymp) were studied as primary outcome parameters. Secondary outcomes included time to radiologic progression (TTPrad) according to CT and safety. In addition, digital contrast-enhanced NMR (DCE-NMR) and contrast-enhanced ultrasound (CEUS) of liver metastases were performed in selected pts. Results: A total of 62 pts (median age 63 yrs, range 35–83 yrs; 31 female [50%], 31 male [50%], ECOG 0 44 pts [71%], ECOG 1 15 pts [26%], ECOG 2 2 pts [3%]) were included in the analysis on an intent to treat basis (ITT). Fortysix pts had no prior systemic treatment (74%). Metastatic sites included liver in 60 pts (97%) in addition to other organs in 20 pts (32%). Only two pts (3%) had exclusively extrahepatic metastases. Following 4 CTC-Grade 4 toxicities [hand-foot-syndrome (HFS) and/or diarrhea] in the first 31 pts (G1) (13%), the starting dose of S was reduced to 200 mg twice daily in the subsequent 31 pts (G2) effectively preventing further severe side effects. Median OS was 10.8 mths (CI 6.1–15.1 mths) in G1 and 14.0 mths (CI 6.4-nd mths) in G2, median TTPrad was 5.0 mths (CI 3.1–8.9 mths) in G1 and 4,5 mths (CI 1.5–6.0 mths) in G2 and TTPsymp was 4.1 mths (CI 3.1–5.2 mths) in G1 and 7.1 mths (CI 3.2–10.6 mths) in G2 (Wilcoxon 0.043), respectively. Conclusions: S at a dose of 200 mg bid is safe in pts with metUvMel predominantly metastatic to the liver and seems to be effective with a median OS of more than 10 mths. Treatment results are encouraging in an orphan malignant disease without established palliative systemic treatment options. A multicenter randomized discontinuation trial with S in pts with metUvMel will be performed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C185.